Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia

From the French Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Saint-Louis Hospital and Université de Paris (R.P.L., F.S.F., C.F., G.S.), and the Adolescent and Young Adult Hematology Unit, Saint-Louis Hospital (F.R.), Paris, the Hematology Department, Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse (C.R., S.T.), Centre Hospitalier Universitaire Lyon Sud, Lyon (F.B., A.P.), Centre Hospitalier Universitaire de Bordeaux, Hôpital Haut-Lévêque, Pessac (E.F., L.C.), the Department of Clinical Hematology, Rennes University Hospital, Rennes (J.-B.M.), Service d'Hématologie, Hôpital Jean Minjoz, Besançon (E.D.), and Hôpital Claude Huriez, Lille (L.T.) - all in France; the Clinical Study Unit, European Society for Blood and Marrow Transplantation (R.P.L., A.K., S.I., S.R.T., I.S.-O., C.F., C.D., A.M.R.), and the Department of Hematology, Leiden University Medical Center (C.J.M.H., J.M.L.T.), Leiden, the Department of Hematology, University Medical Center Utrecht, Utrecht (R.A.P.R.), the Department of Hematology, University Medical Center Groningen, Groningen (M.R.G.), and the Department of Clinical Hematology, Amsterdam University Medical Centers, Academic Medical Center, Amsterdam (E.N.) - all in the Netherlands; the Department of Haematological Medicine, King's College Hospital NHS Foundation Trust (A.K., R.C., A.E.S., P.M., J.C.W.M., G.J.M.), and Barts Health NHS Trust, St. Bartholomew's Hospital (J.C.), London, the Department of Haematology, St. James's University Hospital, Leeds (M.G., T.M., A.H., P.M.), and the Centre for Clinical Haematology, Nottingham University Hospital, Nottingham (N.H.R.) - all in the United Kingdom; the Department of Biology, Università Tor Vergata (S.I.), and the Department of Translational and Precision Medicine, Division of Hematology, Sapienza University (A.P.I., U.L.R.), Rome, Ematologia e Centro Trapianti, IRCCS Ospedale Policlinico San Martino (E.A., M.T.L.), and the Hematology Unit, IRCCS Istituto Giannina Gaslini (E.P., C.D.), Genoa, Unità Operativa Complessa di Ematologia, Unità Operativa Complessa di Fisiopatologia delle Anemie, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan (W.B.), the Department of Clinical Medicine and Surgery, Federico II University, Naples (S.M., L.M., F.C., C.F., A.M.R.), and Ematologia e Trapianto Emopoietico, Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati, Avellino (L.M., C.F., A.M.R.) - all in Italy; University Hospital Donostia, San Sebastián (J.C.V.), the Department of Hematology, Catalan Institute of Oncology Bellvitge Hospital-Hospital Duran i Reynals, L'Hospitalet de Llobregat (A.S.), Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Barcelona (B.X.), and Servicio de Hematología y Hemoterapia, Hospital Universitario y Politécnico La Fe, Valencia (I.J.) - all in Spain; and the Department of Hematology, University Hospital Basel, Basel, Switzerland (B.D., J.R.P.).

The New England journal of medicine. 2022;386(1):11-23
PICO Summary

Population

Patients with severe aplastic anaemia (n= 197).

Intervention

Immunosuppressive therapy plus eltrombopag (n= 96).

Comparison

Immunosuppressive therapy (n= 101).

Outcome

The percentage of patients who had a complete response at 3 months was 10% for patients in the immunosuppressive therapy group, and 22% for patients in the immunosuppressive therapy plus eltrombopag group. At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% for those receiving immunosuppressive therapy, and 68% for those receiving immunosuppressive therapy plus eltrombopag. The median times to the first response were 8.8 months (immunosuppressive therapy group) and 3.0 months (immunosuppressive therapy plus eltrombopag group). The incidence of severe adverse events was similar in all patients.
Abstract
BACKGROUND A single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia. METHODS In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months. RESULTS Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P = 0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Β) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome. CONCLUSIONS The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects. (Funded by Novartis and others; RACE ClinicalTrials.gov number, NCT02099747; EudraCT number, 2014-000363-40.).
Study details
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine